Recent research into rivaroxaban

No reason to expand the indications

  • Rivaroxaban has clearly found its way into Dutch medical practice, for a limited number of registered indications: for venous thrombo-embolism (treatment and prevention) and for the prevention of thrombus formation in patients with atrial fibrillation without cardiac valve disorder or comorbidity and after an acute coronary syndrome, in combination with a platelet aggregation inhibitor.
  • The number of users of rivaroxaban in the Netherlands has shown a surprising increase, considering the fact that its efficacy and safety have hardly ever been compared with usual Dutch care practice.
  • Results of research into the efficacy of rivaroxaban compared with that of acetylsalicylic acid for indications for which it is not registered in the Netherlands (long-term anticoagulation after each venous thrombo-embolism, secondary cardiovascular prevention in combination with acetylsalicylic acid and secondary cardiovascular prevention after a stroke of unknown cause) have been disappointing: the risk of haemorrhages was often found to be higher.
  • As regards the registered indication for rivaroxaban in prolonged anticoagulant therapy up to 30 days after the initial anticoagulant treatment for knee of hip replacement surgery, the use of acetylsalicylic acid (100 mg) has been found to be just as safe and effective as rivaroxaban. This is an interesting finding which warrants further research, especially from the point of view of costs.
  • No direct antagonist of rivaroxaban has been found that can be used in case of overdose or the development of severe haemorrhages.
  • In all, there are still sufficient arguments to remain reticent about prescribing direct oral anticoagulants (DOACs) like rivaroxaban.

  1. Informatorium medicamentorum 2018. KNMP Den Haag. Opgeroepen op 05 12, 2018, via :
  2. Furie B, Furie BCC. Mechanisms of Thrombus Formation. N Engl J Med. 2008 Aug 359(9):938-49. 
  3. Goodman L, Gilman A. Goodman & Gilman's manual of pharmacology and therapeutics. New York: McGraw-Hill Medical. 2014
  4. Nederlands Huisartsen Genootschap. NHG-Standaard Diepe veneuze trombose en longembolie. 2018. Opgeroepen op 06 10, 2018, via:
  5. Schulman S, Kearon  C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr; 3(4)): 692–4.
  6. Kaatz S, Ahmad D, Spyropoulos AC, Schulman S. (). Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost. 2015 Nov; 13(11), 2119-26.
  7. Weitz JI, Lensing AWA, Prins MH, Bauersachs R, Beyer-Westendorf J, Bounameaux H, et al. Rivaroxaban or Aspirin for Extended Treatment of Venous. N Engl J Med. 2017 Mar; 376(13): 1211-1222.
  8. Eikelboom JW, Connolly SJ, Bosch J, Dagenais GR, Hart RG, Shestakovska O, Diaz R, et al. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. N Engl J Med. 2017 Oct; 377(14):1319-1330. 
  9. Hart RG, Sharma M, Mundl H, Kasner SE, Bangdiwala SI, Berkowitz SD, Swaminathan B, et al. Rivaroxaban for stroke prevention after embolic stroke of undertermined source. N Engl J Med. 2018 Jun; 378(23): 2191-2201.
  10. Anderson DR, Dunbar M, Murnaghan J, Kahn SR, Gross P, Forsythe M, et al. Aspirin or Rivaroxaban for VTE Prophylaxis after Hip or Knee Arthroplasty. N Engl J Med. 2018 Feb;378(8):699-707.
  11. Nederlandse Internisten Vereniging. Richtlijn Antitrombotisch beleid. 2015. Utrecht:
  12. Nederlands Huisartsen Genootschap. NHG-Standaard Cardiovasculair risicomanagement. 2012. Opgeroepen op 06 10, 2018, via:
  13. Nederlandse Vereniging voor Neurologie. Herseninfarct en hersenbloeding. Kennisinstituut van Medisch Specialisten. 2017. Via:

The literature refers to the Dutch text


  • mw S. van der Heijden MSc, dr H.J.E.M. Janssens